L-Dopa methyl ester has demonstrated significant antitumor activity in 1) leukemia, 2) P388 leukemia, 3) B-16 melanoma, and 4) C-1300 neuroblastoma. Furthermore, new analogs of L-dopa, specifically 3,4-dihydroxybenzylamine and N-acetyldopamine, exhibited enhanced antitumor activity with decreased neurotoxicity. We have proposed a mechanism of action involving inactivation of DNA polymerase by sulfhydryl group scavenging by dopa quinone. We now propose to 1) prepare analogs of dopa and dopamine in order to increase antitumor activity and diminish neurotoxicity, 2) undertake schedule dependency studies, since preliminary experiments indicate that frequent administration results in a marked enhancement of antitumor response, 3) conduct cell cycle phase sensitivity studies in order to ascertain if DNA synthesis inhibition is a primary site of action, 4) using permeabilized cells, examine directly the incorporation of thymidine triphosphate in order to define the biochemical level at which growth inhibition occurs.